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Biomedical subjects

C Hamilton

Publications and source records attributed to C Hamilton.

At least 19 recordsLinked to original sources

Factors affecting motion characteristics of frozen-thawed stallion spermatozoa.

Five experiments were conducted to evaluate damage incurred in each processing step for cryopreservation of stallion spermatozoa. In Experiment 1, semen was centrifuged for 9 centrifugation times and the percentage of spermatozoa recovered after each treatment was calculated and spermatozoal motion characteristics analysed. Recovery of spermatozoa was > or = 80% when spermatozoa were centrifuged for > or = 10 min. Experiment 2 evaluated spermatozoa cryopreserved at 5 different concentrations in each of 2 extenders (skim milk-egg yolk-glycerol, SM-EYG; and lactose-EDTA, LAC). In SM-EYG, TMOT and PMOT were higher at spermatozoal concentrations of 20, 200 and 400 x 10(6)/ml (51%/41%, 52%/44%, 50%/43%, respectively) than for samples frozen at > or = 800 x 10(6) spermatozoa/ml (41%/35%, 32%/27%; P < 0.05). Spermatozoa frozen in LAC at a concentration of 20 x 10(6)/ml resulted in the highest TMOT and PMOT (43% and 30%, respectively, P < 0.05). The effect of freezing rate on motion characteristics of spermatozoa was evaluated in Experiment 3. The VCL of spermatozoa frozen in SM-EYG was the only parameter affected by freezing rate (P < 0.05). Experiment 4 evaluated motion characteristics after cryopreservation of spermatozoa in different sized straws (0.5 or 2.5 ml) in each of 2 extenders (SM-EYG and LAC). In SM-EYG, PMOT (38%) and VCL (109 microns/s) were highest when spermatozoa were frozen in 0.5 ml straws (P < 0.05). In Experiment 5, spermatozoa thawed immediately after cryopreservation or thawed after storage in liquid nitrogen for 24-48 h were evaluated. There was no effect of length of storage in liquid nitrogen on spermatozoal motion characteristics (P < 0.05). Experiment 6 evaluated the effects of cooling time to 5 degrees C (0, 2.5 and 5 h) on motion characteristics of spermatozoa cryopreserved in 2 extenders (SM-EYG and LAC). TMOT and PMOT were effected by cooling time, and there was a cooling-time-by-extender interaction (P < 0.05). In SM-EYG, TMOT and PMOT were higher if spermatozoa were cooled to 5 degrees C prior to initiation of freezing than if freezing was initiated at 20 degrees C (P < 0.05). A suggested protocol for cryopreservation of stallion spermatozoa would include: 1) centrifugation at 400 g for 14 to 16 min; 2) extension at 23 degrees C with SM-EYG to 400 x 10(6) spermatozoa/ml; 3) cool to 5 degrees C for 2.5 h; 4) package in 0.5 ml straws at 5 degrees C; 5) freeze in liquid nitrogen vapour at -160 degrees C; and 6) thaw for 30 s in 37 degrees C water.

Animals

Oxidized-LDL induced changes in membrane physico-chemical properties and [Ca2+]i of bovine aortic endothelial cells. Influence of vitamin E.

The effects of 3 days' exposure to native and oxidatively modified human low density lipoprotein (LDL and Ox-LDL) on cultured bovine aortic endothelial cell cholesterol content, membrane microviscosity and intracellular free calcium concentration ([Ca2+]i) were studied. Free cholesterol content increased by 35% and 100% in LDL and Ox-LDL treated cells, respectively, these effects being reversed by vitamin E; esterified cholesterol, which rose by 110% in the Ox-LDL group only, was not affected by vitamin E. Membrane microviscosity, measured as the fluorescence polarization of the trimethylammonium derivative of diphenyl-hexatriene, increased by 9% in Ox-LDL treated cells only. This effect was also reversed by vitamin E. Using the calcium sensitive fluorescent dye fura 2-AM, increases in basal [Ca2+]i of 36% in LDL and 81% in Ox-LDL treated cells were observed. The bradykinin mediated increase in [Ca2+]i was enhanced in both the LDL and, to a greater extent, the Ox-LDL group. Vitamin E reversed the effects of LDL on [Ca2+]i but had no influence in the Ox-LDL group. The lipoproteins affected all parameters measured in this study. Oxidized LDL produced reversible and irreversible alterations to the membrane and the [Ca2+]i. All changes associated with LDL were abolished by vitamin E. Such modifications in the physicochemical properties of the membrane and [Ca2+]i could be involved in the initiation of the atherosclerotic process.

Animals

A rapid diagnostic and treatment center for patients with chest pain in the emergency department.

STUDY OBJECTIVE: To evaluate a comprehensive diagnostic 9-hour evaluation (Heart ER Program) for patients with possible acute ischemic coronary syndromes. DESIGN: Retrospective review of consecutive patients. SETTING: Urban tertiary care emergency department. PARTICIPANTS: A total of 1,010 patients with symptoms suggestive of acute ischemic coronary syndrome was enrolled in the Heart ER Program over the first 32 months of operation. Patients with history of coronary artery disease, hemodynamic instability, acute ST-segment elevation or depression of more than 1 mm, or a clinical syndrome consistent with unstable angina were directly admitted to the hospital. INTERVENTION: Patients underwent serial testing for creatine kinase (CK-MB) on presentation to the Heart ER and 3, 6, and 9 hours later with continuous 12-lead ECGs/serial ST-segment trend monitoring for 9 hours. Two-dimensional echocardiography and graded exercise testing were performed in the ED after the 9-hour evaluation period. RESULTS: Of 1,010 patients, 829 (82.1%) were released home from the ED; 153 (15.1%) required admission for further cardiac evaluation. Fifty-two of 153 (33.9%) admitted patients were found to have a cardiac cause for their symptoms; 43 had acute ischemic coronary syndromes (12, acute myocardial infarction; 31, angina or unstable angina). CONCLUSION: The Heart ER program provides an effective method for evaluating low- to moderate-risk patients with possible acute ischemic coronary syndrome in the ED setting.

Adult

Workload and use factor of medical linear accelerators in radiotherapy.

An important factor in the design of primary protective barriers is the use factor. The present study was aimed at obtaining historical data on the use factor of two dual modality linear accelerators in a radiotherapy department. Gantry angle, field size, and beam modifiers were recorded for all radiation qualities in use at two medical linear accelerators with 6 MV and 18 MV x-rays and multiple electron energies ranging from 4 MeV to 20 MeV. The data for one year of clinical use was extracted from a record and verifying system and an estimate of the physics workload on the machines was obtained by going through the quality assurance records and machine log books. Of the total dose of approximately 37,000 Gy delivered in one year at isocenter on each unit 80% was given as 6 MV x-rays. As can be expected, most x-ray beams were directed at the four cardinal gantry angles with the angular distribution for 6 MV and 18 MV x-rays being very similar. Electron fields were broadly distributed around the gantry pointing down position. Less than 25% of all clinical x-ray treatment fields extended beyond a field size of 200 cm2.

Blood Component Transfusion

Peptides related to thyrotrophin-releasing hormone (TRH) in human prostate and semen.

The TRH-related peptide, pGlu-Glu-ProNH2, which was first identified in rabbit prostate has recently been named fertilization-promoting peptide (FPP) because of its ability to enhance the in vitro fertilizing potential of mouse epididymal spermatozoa. This study set out to examine the nature of the TRH-related peptides in human prostate and semen but, first, the optimal conditions for collection of semen samples were investigated. FPP was degraded slowly (t1/2 = 163 min, S.E. +/- 51.3, n = 6) in seminal plasma which has allowed us to measure accurately the concentrations of FPP, after extraction of the peptide in acidified acetone precisely 5 min after ejaculation. In this way, high levels of FPP (mean: 49.5 nmol/l) were detected in normal human semen, from young men, although other TRH-related peptides did not appear to be present. We have also examined the TRH-related peptides present in prostate samples from clinical patients both with and without evidence of benign prostatic hyperplasia (BPH), by ion-exchange chromatography followed by radioimmunoassay. Substantial concentrations of FPP were observed in normal (4.10 pmol/g tissue, S.E. +/- 1.46) and BPH prostate (6.27 pmol/g tissue, S.E. +/- 1.65). In addition, a second, neutral TRH-immunoreactive peptide was always detected in BPH tissue (7.40 pmol/g tissue, S.E. +/- 1.98) with only low levels generally present in normal prostate. The possibility that the presence of high levels of the neutral peptide in prostate may be used as an indicator of the onset of BPH deserves further scrutiny.

Adult

Bioaccumulation of aromatic hydrocarbons from sediments: a dose-response study with flounder (Pseudopleuronectes americanus).

Pseudopleuronectes americanus were chronically exposed to Hibernia crude oil in sediments, for 4 months. Oil was added to sediments at five concentrations between 0.09 and 4.5 mg/g (dry weight) and was 0.10-0.90 mg/g, at the termination of the exposure. Bioaccumulation measured in terms of fluorescence or in terms of the concentration of specific aromatic targets, increased with dosage. Accumulation of hydrocarbons was observed in muscle tissue (0.22 microgram/g, dry weight), when concentration of the sum of 27 polycyclic aromatic compounds (PAC) in sediments was of 0.65 microgram/g (E-50), at the end of the 4-month period. Of the 27 parental and alkylated polycyclic aromatic compounds analyzed, alkylated naphthalenes predominated in muscle (90-100%) and in sediments (30-60%). Bioaccumulation factors were derived for 13 compounds detected in muscle, at the three higher exposures. Liver concentrations (fluorescence) were higher than in muscle, but did not display a noticeable dose-response. Several alkylbenzenes, a C-2 biphenyl and C-4 acenaphthene were also detected in muscle extracts. The development of dose-response relationships for polycyclic aromatic hydrocarbons (PAH) present in sediment, in relation to bioaccumulation in flatfish, is of major interest for evaluating the environmental effects of oil contamination.

Animals

Determinants of low systemic vascular resistance during cardiopulmonary bypass.

Although low systemic vascular resistance occurs during normothermic and hypothermic cardiopulmonary bypass, the determinants of depressed systemic vascular resistance and its effect on outcomes are unknown. To assess the predictors and clinical effects of low systemic vascular resistance, 555 patients undergoing isolated coronary artery bypass grafting were evaluated prospectively. The extent of low systemic vascular resistance during bypass was estimated by the amount of the vasoconstrictor phenylephrine administered: group 1, 0 to 160 micrograms; group 2, 161 to 800 micrograms; group 3, more than 800 micrograms. Multivariate analysis identified bypass temperature, bypass time, and ventricular function as determinants of low systemic vascular resistance. Patients on normothermic bypass accounted for 65% of the patients in group 3 and only 34% of the patients in group 1 (p < 0.0001). The bypass time was longer in the patients in group 3 (97 +/- 28 minutes) than in the patients in group 1 (89 +/- 24 minutes; p < 0.006). Patients with a preoperative left ventricular ejection fraction of 0.40 or less required less phenylephrine during cardiopulmonary bypass (498 +/- 68 micrograms) than did patients with a fraction exceeding 0.40 (1,087 +/- 88 micrograms; p < 0.001). By multivariate analysis, advanced age and the presence of peripheral vascular disease were found to decrease the likelihood of low systemic vascular resistance during normothermic bypass. Diabetes, the left ventricular ejection fraction, the bypass time, and the total cardioplegia infused were found to influence the likelihood of low systemic vascular resistance during hypothermic bypass. Patients in group 3 had a higher cardiac index and lower-mean arterial pressure and systemic vascular resistance postoperatively. In those patients who received a left internal mammary artery graft, the incidences of the low-output syndrome (group 1, 4.9%; group 3, 2.7%; p = not significant) and myocardial infarction (group 1, 1.4%; group 3, 1.8%; p = not significant) were not influenced by the amount of phenylephrine infused during cardiopulmonary bypass. In those patients who were at high risk of suffering a stroke preoperatively, the hypotension induced by the low systemic vascular resistance and its treatment with phenylephrine was not associated with an increased incidence of stroke (group 1, 5.8%; group 3, 2.8%; p = not significant).

Aged

Patient compliance with short-term topical aural antibiotic therapy.

Little is known about patient compliance with topical aural antibiotic regimens. The compliance of 50 patients with unilateral otitis externa attending an otolaryngology clinic was studied by comparing the weight of dispensed topical ear preparations before and after completion of a 7-day-course of treatment. A standard was obtained from controlled administration of the preparation under laboratory conditions and the performance of different delivery systems evaluated. Thirty-seven patients re-attended for review with their medication. A total of 34 of 50 patients entering the study (70%) satisfied conventional criteria for compliance. However, over-use of preparations was common and stricter criteria are proposed and applied. Compliance was significantly increased when someone other than the patient administered the preparation.

Administration, Topical

Pharmacokinetics of the anticancer agent sulofenur in mice, rats, monkeys, and dogs.

The absorption and pharmacokinetics of sulofenur [N-(indan-5-sulfonyl)-N'-(4-chlorophenyl)urea, LY186641] and its major metabolites were examined in mice, rats, monkeys, and dogs. The compound is a diarylsulfonylurea currently being evaluated as an oncolytic agent in phase I and II trials. In all species, sulofenur was well absorbed after an oral dose, but over a prolonged period, and sulofenur exhibited a fairly long half-life of elimination from plasma. These values ranged from 6 h in rats up to 30, 110, and 200 h in mice, monkeys, and dogs, respectively, at doses (240-1000 mg/m2) within the range of those used in clinical trials. Experiments describing the high degree of binding of sulofenur to plasma proteins (consistently > 99%) help to explain these relatively long half-lives. There is, however, a large difference between these plasma half-lives in the species studied. Sulofenur was previously found to be extensively metabolized to products that are excreted primarily into the urine. In this study, its major metabolites, which are found mainly in the urine, were also minor components of the drug-related material (< 10% of the sulofenur concentrations) in the plasma of rats treated with sulofenur. The absorption, binding characteristics, and elimination of these major metabolites after their administration to rats were also compared with sulofenur.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Strain gauge plethysmography for the detection of deep venous thrombosis.

Deep venous thrombosis is a widely recognized medical problem which results in significant morbidity and mortality. Venography is the current 'gold standard' diagnostic test for deep venous thrombosis; however it is costly, invasive and is unnecessarily performed in 50% of cases. This paper describes a self-contained, non-invasive system for automatic venous occlusion plethysmographic measurement and analysis. An examination of 274 symptomatic limbs was conducted using strain gauge plethysmography and a subsequent venographic examination was then performed. The plethysmographic results were then compared with venography so as to develop a means of discrimination for thrombotic and non-thrombotic limbs. Strain gauge plethysmography using the Belfast DVT Screener yielded a sensitivity of 100% and a sensitivity of 66.3% for proximal segment DVT. The efficacy of the discriminatory algorithm was then tested for the diagnosis of DVT in a further 101 symptomatic patients. A sensitivity of 94.7% and a specificity of 81.7% were observed for strain gauge plethysmography for proximal segment thrombosis in this patient group. The Belfast DVT Screener is highly sensitive for deep venous thrombosis and may be used to reduce the need for venography, which is of benefit to both the patient and clinician.

Adult

Vascular smooth muscle response to ouabain. Relation of tissue Na+ to the contractile response.

Smooth muscle responses to Na+ pump inhibition are thought to reflect two elements: a neurogenic contribution, involving catecholamine release from nerve terminals, and a myogenic response, attributed to relations between pump activity, [Na+]i, and [Ca2+]i. In the present study, we describe the time course and magnitude of cell Na+ changes, assessed by two methods, atomic absorption and nuclear magnetic resonance spectroscopy during the myogenic contractile response of rabbit aorta strips to ouabain. A threshold concentration of 3 x 10(-7) mol/L induced a gradual rise in [Na+]i. Both methods showed an essentially identical monotonic rise over 4 to 8 hours from a baseline level of 8 to 10 mmol/L water to a peak, which was approximately fivefold higher. The neurogenic (rapid) and myogenic (delayed and gradual) contractile responses were temporally distinct. Ouabain at 10(-7) mol/L, a concentration 10- to 100-fold lower than the threshold for catecholamine-dependent rapid-onset responses, induced only a delayed and gradual contractile response, which reached a maximum at 6 to 8 hours. With 10(-6) mol/L ouabain, the delayed response of 1.6 +/- 0.2 g peaked at 7.3 +/- 1.1 hours and was sustained for 16 hours. The time course was similar to that for change in [Na+] but somewhat later. Ouabain at 10(-5) and 10(-4) mol/L induced a delayed response that was identical in magnitude but also induced an early rapid contractile response, which was prevented by reserpine or phentolamine pretreatment. These agents did not influence the delayed response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Increased urinary excretion of pyridinium cross-links in cancer patients.

Pyridinoline (PYD) and deoxypyridinoline (DPD), two collagen-based cross-links found in bone, were measured by high-performance liquid chromatography in urine samples from 65 control subjects and 97 patients with either untreated or progressive cancer. Patients with cancer had significantly (P < 0.001) higher urine concentrations of PYD and DPD than did control subjects. Both cross-links were increased in cancer patients with and without clinically detectable bone metastases, although patients with bone and liver involvement had higher mean concentrations. The mean concentrations of both cross-links were also significantly higher in the urine samples of inpatients than in an outpatient ambulatory population. These findings suggest that the measurement of PYD and DPD in urine may be useful in assessing bone metastases and bone resorption in cancer patients.

Adult

Age-related changes in human blood lymphocyte subpopulations.

Flow cytometric analysis of major lymphocyte populations and their subsets reveals age-related changes in the cellular human immune system. Immunophenotypic markers were evaluated in 110 normal pediatric subjects, divided into groups of newborn infants, infants aged 2 days to 11 months, and children aged 1 to 6 years and 7 to 17 years; results were then compared with those obtained from 101 normal adults aged 18 to 70 years. Comparisons among age groups from newborn infants through adults reveal progressive declines in the absolute numbers of leukocytes, total lymphocytes, and T, B, and natural killer (NK) cells. The percentages of T cells within the total lymphocyte population increase with age, in both CD4+ and CD8+ subsets. Percentages of B and NK cells are higher in newborn infants than in adults. The expression of the activation markers interleukin-2R and HLA-DR on T cells increases with age, as does the NK-associated expression of CD57 on CD8 cells. The proportions of B lymphocytes that coexpress CD5 or CDw78 decrease with age, whereas expression of Leu-8 and CD23 increases. The proportion of CD4 cells bearing the CD45RA and Leu-8 markers is consistently lower in adults than in children. These data may serve as a reference range for studies of pediatric subjects.

Adolescent

Loco-regional recurrence and survival after wide local excision, radiotherapy and axillary clearance for early breast cancer.

After breast conservation for early breast cancer which comprised wide local excision, axillary clearance and radiotherapy to the breast, 145 women have been followed prospectively for a median of 42 months. Local recurrence occurred in 11 (7%) and axillary recurrence in three (2%). Distant recurrence has occurred in 32 and accounted for 80% of all first recurrences. Local treatment failure has occurred in three women and would not have been prevented by mastectomy. Loco-regional recurrence in the absence of preceding or synchronous distant disease was unusual and did not pose a significant clinical problem.

Adult